The effect of hepatocyte enlargement on the hemodynamic characteristics of the isolated perfused rat liver preparation.
The influence of hepatocyte enlargement on intrahepatic hemodynamics was assessed in the isolated perfused rat liver preparation (IPRL) using two experimental models: hypotonic liver cell swelling and phenobarbitone-induced hepatocyte hypertrophy. The analysis of pressure-flow data obtained from the portal vascular bed over a flow range of 0 to 70 mL/min in the presence of a maximally-effective concentration of the vasodilator agent papaverine hydrochloride (6 x 10(-4) mol/L) enabled the calculation of P0, an estimate of the pressure required to passively distend the intrahepatic vasculature, and Gmax, the maximal portal vascular conductance. By comparison with an isotonic perfusion medium (Krebs-Henseleit buffer [KH] containing 2.5% bovine serum albumin [BSA]), perfusion with a hypotonic medium induced a significant increase in mean hepatocyte cross-sectional area (H(A)) (590 +/- 21 vs. 324 +/- 23 microm(-2), p < .05), a fall in Gmax (0.39 +/- 0.08 vs. 2.02 +/- 0.18 mL/min/g/mm hg, P < .001), and an increase in P0 (2.96 +/- 0.38 vs. 1.58 +/- 0.07 mm hg, P < .001). Phenobarbitone administered in drinking water (0.5 g/L) over a period of 60 days also induced a significant degree of hepatocyte enlargement (HA, 510 +/- 29 microm2, P < .05). On day 7, portal pressure measured in vivo in this group was significantly elevated compared with untreated controls (10.5 +/- 0.3 vs. 8.4 +/- 0.2 mm hg, P < .001), while in the IPRL Gmax was reduced (0.48 +/- 0.01 mL/min/g/mm hg, P < .001), and P0 was increased (2.23 +/- 0.17 mm hg, P < .05). However, with continued phenobarbitone treatment portal pressure, Gmax and P0 returned toward control values. The results confirm that hepatocyte enlargement is associated with a significant disturbance of intrahepatic hemodynamics but also that some adaptation occurs if hepatocyte enlargement is sustained over a prolonged period of time.
Grossman
H J
HJ
Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Grossman
V L
VL
Bhathal
P S
PS
D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D006984:Hypertrophy / Q000139:chemically induced / Q000503:physiopathology; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007038:Hypotonic Solutions; D010208:Papaverine; D010634:Phenobarbital